Circulating tumour DNA and melanoma survival: A systematic literature review and meta-analysis

We reviewed and meta-analysed the available evidence (until December 2019) about circulating tumour DNA (ctDNA) levels and melanoma patients survival. We included twenty-six studies (>2000 patients overall), which included mostly stage III-IV cutaneous melanoma patients and differed widely in terms of systemic therapy received and somatic mutations that were searched. Patients with detectable ctDNA before treatment had worse progression-free survival (PFS) (summary hazard ratio (SHR) 2.47, 95 % confidence intervals (CI) 1.85-3.29) and overall survival (OS) (SHR 2.98, 95 % CI 2.26-3.92), with no difference by tumour stage. ctDNA detectability during follow-up was associated with poorer PFS (SHR 4.27, 95 %CI 2.75-6.63) and OS (SHR 3.91, 95 %CI 1.97-7.78); in the latter case, the association was stronger (p = 0.01) for stage IV vs. III melanomas. Betweenestimates heterogeneity was low for all pooled estimates. ctDNA is a strong prognostic biomarker for advancedstage melanoma patients, robust across tumour (e.g. genomic profile) and patients (e.g. systemic therapy) characteristics.

Automated summary

This study reviewed and analyzed evidence on the relationship between ctDNA levels and survival in melanoma patients, finding that detectable ctDNA is associated with worse outcomes. The prognostic value of ctDNA was consistent across different characteristics of both tumors and patients.